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T型钙通道阻滞剂对成年C57BL/6J小鼠耳蜗毛细胞的保护作用

Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers.

作者信息

Yu Ya-Feng, Wu Wen-Ying, Xiao Gen-Sheng, Ling Hong-Yang, Pan Chen

机构信息

Department of Otolaryngology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

出版信息

Exp Ther Med. 2016 Mar;11(3):1039-1044. doi: 10.3892/etm.2016.2970. Epub 2016 Jan 8.

Abstract

The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6-8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24-26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24-26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected.

摘要

本研究旨在利用C57BL/6J小鼠模型,研究T型钙通道阻滞剂对老年性耳聋的保护作用。采用逆转录-定量聚合酶链反应评估6-8周龄C57BL/6J小鼠耳蜗中三种T型钙通道受体亚基的表达。结果证实这三种亚基在耳蜗中表达。此外,在用米贝地尔、贝尼地平或生理盐水处理4周的小鼠中,研究了T型钙通道阻滞剂保护24-26周龄C57BL/6J小鼠耳蜗毛细胞的能力。使用听性脑干反应(ABR)检测听力阈值差异,同时使用畸变产物耳声发射(DPOAE)测试测量振幅差异。ABR测试结果显示,与生理盐水处理组相比,米贝地尔处理组和贝尼地平处理组在24 kHz时的听力阈值显著降低。在11.3和kHz的F2频率下,米贝地尔处理组的DPOAE振幅比生理盐水处理组增加。此外,在13.4 kHz的F2频率下,贝尼地平处理组的DPOAE振幅比生理盐水处理组增加。米贝地尔处理组外毛细胞(OHC)的损失不明显;然而,内毛细胞(IHC)的静纤毛排列紊乱且稀疏。总之,这些结果表明,连续四周给予T型钙通道阻滞剂可能改善24-26周龄C57BL/6J小鼠在24 kHz时的听力。给予T型钙通道阻滞剂可显著改变C57BL/6J小鼠OHC的功能和形态;然而,IHC未受影响。

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